1. Field of the Invention
The invention relates to computation of interatomic and intermolecular interactions. Embodiments of the invention are applicable to chemical, physical, and biological research, and to the development of new pharmaceutical compounds.
2. Description of the Related Art
Over the last few years, significant advances have been made in predicting, studying, and quantifying the nature of interatomic and intermolecular interactions with the use of computer simulations. Although from a purely scientific point of view, such computer simulations can be useful in testing and validating a theory concerning the nature of these interactions, computer simulations find especially useful application in reducing the time required to develop new materials with desirable properties. Materials which may be developed with additional efficiency through the use of computer simulations include polymers, pesticides, herbicides, pharmaceuticals, semiconductor materials for integrated circuits, and petrochemicals to name a few.
Several modeling techniques are used in these environments. Typically, the model selected provides a user of the model with a particular compromise between physical accuracy and the computing resources required to run the model. Ab initio quantum mechanical calculations can be performed with a high degree of accuracy, but are very expensive in terms of the computer time required to perform them. In those fields described above, where new polymers, drugs, etc. are being developed, it is more useful to use modeling techniques which require less investment in computing resources, so that more candidate materials or molecules can be analyzed in a shorter time period for the properties desired.
Thus, it has become common to model interactions between groups of atoms, molecules, proteins, and other structures by defining an atom to atom potential which acts between the atoms of the system being analyzed. Generally speaking, the atomxe2x80x94atom potential defines the energy of the atomic system as that energy varies with the coordinates of the atoms. Intramolecular xe2x80x9cbondedxe2x80x9d interactions may include terms defining energy as a function of bond lengths, bond angles, torsion angles, and out-of plane coordinates. Intermolecular, or non-bonded potentials, typically include van der Waals interactions and electrostatic interactions. The benefit of these force field models is that the behavior of the atoms in the model is calculated using classical mechanics and electrostatics, which is significantly simpler computationally than performing the more mathematically complex quantum mechanical calculations.
However, because the systems being analyzed do not in fact behave classically, the models include parameters associated with the force field terms which are selected to fit known quantum mechanical molecular and atomic interactive behavior. In this way, a classically formulated force field is used to approximate quantum mechanical behavior at the atomic and molecular scale. A variety of force field models are known. Force field models are provided, for example, in U.S. Pat. No. 5,612,894 to Wertz, and in xe2x80x9cDREIDING: A Generic Force Field for Molecular Simulations,xe2x80x9d J. Phys. Chem. 94, 8897-8909 (1990). An additional force field model, nicknamed xe2x80x9cCFFxe2x80x9d, and which was developed by several of the inventors of the subject matter of the present application, is described in J. Comp. Chem 15, 162-182 (1994), and in J. Am. Chem. Soc. 116, 2515-2525 (1994). The disclosure of U.S. Pat. No. 5,612,894 and the Journal articles described above are hereby incorporated by reference in their entireties.
It can be appreciated that the selection of appropriate parameters and force field functional dependencies is a significant factor in the success of the model. Furthermore, the number of fitted parameters used in the model relative to the number of measurable or ab initio calculable values relevant to the system being modeled should be as low as possible. A model with as many fitted parameters as observables has little predictive value for systems which were not used in initially creating the fitted parameters.
Currently, most force fields treat interatomic electrostatic interactions using a partial charge model in which each atom is assigned a net charge and Coulomb""s Law is used to calculate forces on each atom due to the other atoms of the system. The DRIEDING and CFF force fields mentioned above are examples. Another alternative which has been devised is to model a molecule as a set of bond centered dipoles. Neither treatment adequately models the interaction between atoms and the local electric fields. Accordingly, new force field parameterization schemes are needed to increase agreement with experiment, to maximize the number of observables relative to the number of parameters, and to limit the necessity of performing computationally expensive calculations.
The invention includes methods of evaluating a candidate molecule for suitability for a particular purpose. In one embodiment, the method includes selecting a candidate molecule and calculating a dipole moment induced in a first atom of the candidate molecule from a local electric field, wherein the induced dipole moment may be non-parallel to the local electric field. Using the calculated dipole moment, one or more physical properties of the candidate molecule may be predicted.
In another embodiment, a method according to the invention comprises parameterizing electrostatic behavior of the candidate molecule with a plurality of atomic parameters associated with at least one atom of the molecule, wherein the plurality of atomic parameters includes elements of an anisotropic atomic dipole polarizability tensor. The method also includes determining a dipole moment induced in the atom due to a local electric field using the atomic dipole polarizability tensor and predicting one or more physical properties of the candidate molecule using the induced dipole moment.
Embodiments of the invention also include apparatus for modeling the geometry and energy of interaction between first and second groups of atoms. The apparatus may comprise a memory storing an anisotropic atomic dipole polarizability tensor for at least one of the first group of atoms. Also provided may be a processor for (1) modeling an electric field produced at least in part by the first and second groups of atoms, (2) retrieving the anisotropic dipole polarizability tensor, and (3) calculating a dipole moment induced in an atom of the first group by the electric field, and (4) calculating an interaction energy between the first and second groups of atoms which includes a contribution from the induced dipole moment. The apparatus may further include an output device for reporting the calculated interaction energy.
Another embodiment of the invention is a computer readable media having stored thereon commands which cause a general purpose computer to perform a method of modeling interactions between a first group of one or more atoms and a second group of one or more atoms. In one embodiment, the method comprises retrieving, for at least one of the first group of atoms, elements of an anisotropic atomic dipole polarizability tensor from a data storage device, modeling an electric field which is dependent on a relative orientation and separation of the first group of atoms and the second group of atoms. The method further includes calculating a dipole moment induced in the atom of the first group from the electric field using the anisotropic polarizability tensor, calculating an interaction energy between the first group of atoms and the second group of atoms which includes a contribution from the induced dipole moment, and outputting the interaction energy.